The document titled “Review: N1-methyl-pseudouridine (m1Ψ): Friend or foe of cancer?” authored by Alberto Rubio-Casillas and colleagues, provides a comprehensive review of the role of N1-methyl-pseudouridine (m1Ψ) in the context of cancer, particularly focusing on its implications when used in mRNA vaccines, such as those developed for COVID-19. The review highlights the rapid development and deployment of mRNA vaccines as a response to the COVID-19 pandemic, emphasizing the innovative technology behind these vaccines and their potential beyond infectious disease prevention, including cancer treatment.
The review discusses the mechanism of mRNA vaccines, which utilize lipid nanoparticles (LNPs) to deliver mRNA into cells, instructing them to produce a specific protein that triggers an immune response. However, the stability and immunogenicity of mRNA vaccines are enhanced by incorporating modified nucleosides, such as m1Ψ, which is used to replace uridine in the mRNA sequence. This modification is shown to increase the stability of the mRNA and reduce its recognition by the immune system as a foreign pathogen, thereby enhancing the vaccine’s efficacy and safety.
Despite these advantages, the review raises concerns about the potential unintended consequences of using m1Ψ-modified mRNA vaccines, particularly in the context of cancer. It presents evidence suggesting that m1Ψ incorporation into mRNA vaccines could impair early interferon signaling pathways, which are crucial for antitumor immunity. Specifically, the review cites studies indicating that m1Ψ-modified mRNA vaccines may inhibit the activation of pattern recognition receptors (PRRs) and the RIG-I signaling pathway, both of which play critical roles in the immune system’s ability to detect and respond to cancer cells.
Furthermore, the review discusses research findings that suggest m1Ψ-modified mRNA vaccines could promote cancer growth and metastasis in certain models. It highlights a study where m1Ψ-modified mRNA vaccines stimulated cancer growth and metastasis in a melanoma model, contrasting with non-modified mRNA vaccines that induced opposite effects. This evidence leads the authors to caution against the use of m1Ψ-modified mRNA vaccines in clinical trials for cancer or infectious diseases without further investigation into their potential to suppress immune responses and promote cancer development.
In conclusion, while m1Ψ-modified mRNA vaccines represent a significant advancement in vaccine technology with proven efficacy against COVID-19, the review underscores the need for further research to fully understand their implications for cancer development and treatment. The authors suggest that future clinical trials should consider using mRNA vaccines with lower percentages of m1Ψ modification to avoid potential immune suppression and unintended promotion of cancer growth[1].
Citations:
[1] Correctedproof-N1-methyl-pseudouridine_240429_182136.pdf https://ppl-ai-file-upload.s3.amazonaws.com/web/direct-files/13640070/79f8679a-9735-46d8-a0a0-b328fddb3d45/Correctedproof-N1-methyl-pseudouridine_240429_182136.pdf
[2] N1-methyl-pseudouridine is incorporated with higher fidelity … https://www.nature.com/articles/s41598-022-17249-1
[3] N1-methylpseudouridine found within COVID-19 mRNA vaccines … – NCBI https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9376333/
[4] Influence of N1-Methylpseudouridine in Guide RNAs on CRISPR/Cas9 … https://www.mdpi.com/1422-0067/24/23/17116
[5] The Role of N1-Methylpseudouridine in COVID-19 Vaccines https://pubs.acs.org/doi/10.1021/acscentsci.1c00197
[6] N1-methyl-pseudouridine in mRNA enhances translation through eIF2α … https://academic.oup.com/nar/article/45/10/6023/3045849
[7] N1-methylpseudouridylation of mRNA causes +1 ribosomal frameshifting https://www.nature.com/articles/s41586-023-06800-3
[8] N1-Methylpseudouridine substitution enhances the performance of … https://academic.oup.com/nar/article/48/6/e35/5742781
[9] Review: N1-methyl-pseudouridine (m1Ψ): Friend or foe of cancer? https://www.sciencedirect.com/science/article/abs/pii/S0141813024022323
